A 41-year-old woman with metastatic melanoma was admitted to the hospital because of syncopal episodes, which had developed after the administration of an experimental chemotherapy agent that targeted Notch signaling, as part of a phase I clinical trial. Cardiac monitoring revealed recurrent episodes of polymorphic ventricular tachycardia correlating with the patient's syncope. Investigations into the cause of the arrhythmia led to the discovery of metastatic lesions within the left ventricular myocardium. In presenting this case of polymorphic ventricular tachycardia as the antemortem clinical manifestation of metastatic melanoma involving the heart, we discuss the importance of recognizing that cardiac metastases can manifest themselves as arrhythmias in patients with malignant melanoma who are undergoing active anticancer treatment.